Electronic Theses and Dissertations

Date of Award

1-1-2020

Document Type

Dissertation

Degree Name

Ph.D. in Pharmaceutical Sciences

First Advisor

David A. Colby

Second Advisor

Sudeshna Roy

Third Advisor

Robert J. Doerksen

School

University of Mississippi

Relational Format

dissertation/thesis

Abstract

ABSTRACT The introduction of fluorine or fluorine containing moieties in pharmaceuticals may increase metabolic stability, binding affinity, bioavailability, lipophilicity, selectivity for targets, and fluorine-labelled groups can be used as imagining probes, i.e. in positron emission tomography (PET). Within the past decade, approximately 20% of all marketed pharmaceuticals contain fluorine and in 2018 alone 36% of the top 50 selling drugs on the market contained one or more fluorine atoms. Fluorinated reagents also plays an important role in the development of methods to introduce unique groups into an organic molecule, such as fluorination and methylenation. In this work, the scope of the trifluoroacetate release reaction was expanded to generate fluorinated lactam intermediates in oder to introduce an α-methylene into a lactam for the purposes of synthesizing L-γ-methyleneglutamine and amide derivatives. A fluorinated reagent was designed to allow the synthesis of compounds containing an α-fluoro-α,β-unsaturated carbonyl group and we attempt to produce organic molecules containing heavily fluorinated methylene carbons such as fluorotrifluoromethyl groups.

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